A Program of research is outlined in the area of pancreatic islet development and regeneration that incorporates a gene/protein discovery program, studies in transcription regulation and cell signaling and addresses the practical goal of engineering beta-cell for transplantation into human subjects through expansion and differentiation ex vivo: PROJECT 1 (Hutton/Duncan): Proteomic and Genomic Analysis of the Developing Endocrine Pancreas. PROJECT 2 (Sussell/Lee): Analysis of the Functions of NeuroD and Nkx2.2 in the Maintenance and Regeneration of the Adult Islet. PROJECT 3 (Levine/Stuart): Human beta-Cell Lines. PROJECT 4 (Jensen): Induction of endocrine neogenesis of endocrine neogenesis from adult pancreas. Two Cores are supported one in are of Administration Informatics), a second providing services to all the projects in the area beta-cell isolation and function analysis. The project directly addresses 2 of the 6 target areas of scientific investigation outlined in the Beta Cell Biology Consortium (beta cell development/cell culture of scientific investigation outlined in the Beta Cell Biology Consortium (beta cell development/cell culture model of the human pancreatic-beta cell). In addition they will generate data using methodologies of relevance to two further aims in the RFA (identification of stem/progenitor cells/evaluation of pancreatic islets for transplantation). The proteomic and genomic approach used in Project 1 will produce a wealth of data that will be placed on a web site supported by the informatics component of Core A that will be accessible for mining by Consortium members and the diabetes research community at large. The principal investigators and co-investigators include both senior and more junior investigators who come from a wide range of disciplines (biochemistry/genetics/molecular biology/cell biology/developmental biology) linked by the common goal of producing cell-based therapy for type 1 diabetes. The Program will be located principally at the Barbara Davis Center for Childhood Diabetes in Denver which will provide further interactions with clinicians, clinical researchers and basic scientists in the area of immunology, human genetics and transplant biology. The BDC is a NIH Diabetes and Endocrine Research Center that will provide support for the Program through Animal Resources, Cytometry, Molecular Resources and a Clinical Core.